512825-94-4Relevant articles and documents
Pharmacophore-based virtual screening for identification of negative modulators of GLI1 as potential anticancer agents
Manetti, Fabrizio,Stecca, Barbara,Santini, Roberta,Maresca, Luisa,Giannini, Giuseppe,Taddei, Maurizio,Petricci, Elena
supporting information, p. 832 - 838 (2020/10/07)
Starting from known GLI1 inhibitors, a pharmacophore-based virtual screening approach was applied to databases of commercially available compounds with the aim of identifying new GLI1 modulators. As a result, three different chemical scaffolds emerged that were characterized by a significant ability to reduce the transcriptional activity of the endogenous Hedgehog-GLI pathway and GLI1 protein level in murine NIH3T3 cells. They also showed a micromolar antiproliferative activity in human melanoma (A375) and medulloblastoma (DAOY) cell lines, without cytotoxicity in non-neoplastic mammary epithelial cells.
Discovery, structure - Activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase
Patnaik, Samarjit,Zheng, Wei,Choi, Jae H.,Motabar, Omid,Southall, Noel,Westbroek, Wendy,Lea, Wendy A.,Velayati, Arash,Goldin, Ehud,Sidransky, Ellen,Leister, William,Marugan, Juan J.
experimental part, p. 5734 - 5748 (2012/08/07)
A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease. This article not subject to U.S. Copyright. Published 2012 by the American Chemical Society.
